This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Like proteins, RNA folds into well-defined three-dimensional structures required for function. The RNA folding problem aims to understand the molecular and dynamic principles upon which RNA structures are built. Solving the RNA folding problem requires knowledge of the structure of folding intermediates. Our long-term goal is to determine the structures of a series of equilibrium and kinetic folding intermediates to fully delineate an entire folding pathway for different tertiary RNAs. Our short term goal is to establish the feasibility of the cryo-EM technique for structure studies of native and folding intermediates of RNAs weighing less than 100 kDa.